The present invention relates to a novel synthetic hexapeptide which has ligand binding specificity of the Leukocyte Response Integrin (LRI) expressed by human neutrophils.
Phagocytes express several members of the integrin superfamily of adhesive receptors which mediate cell-matrix and cell-cell adhesion (for review see Reference no. 1, appended hereto). These include members of both the VLA (.beta..sub.1) family (2,3) and the well-described Leu-CAM (.beta..sub.2) family (1). In addition to these molecules, there exists a novel integrin expressed by human neutrophils (PMN) and monocytes which is referred to as the Leukocyte Response Integrin (LRI) (4-6). Structural and immunologic characteristics of LRI suggest that it is a previously undescribed integrin. However, LRI is most closely related to the .beta..sub.3 integrin family (cytoadhesins) (4-6). It possesses immunologic cross-reactivity with the platelet antigen gpIIIa (.beta..sub.3) and a monoclonal antibody against .beta..sub.3 (mAb 7G2) can abrogate LRI-mediated functions (6). mAb 7G2 inhibits Arg-Gly-Asp (RGD)-stimulated phagocytosis by both PMN and monocytes (6) as well as PMN adhesion and chemotaxis to an RGD-containing peptide derived from the basement membrane protein, entactin (7). In addition, LRI is physically and functionally associated with a separate 50 kd plasma membrane antigen, Integrin-associated Protein (IAP) (6). Like mAb 7G2, monoclonal and polyclonal antibodies against IAP inhibit RGD-stimulated phagocytosis by PMN and monocytes (5,6) and PMN adhesion and chemotaxis to the RGD entactin peptide (7). Thus, it is believed that LRI and IAP, as a complex, constitute a signal transduction unit for the activation of phagocytes by RGD-containing adhesive proteins
Several adhesive proteins containing RGD sequences can transduce signals for PMN activation via LRI and IAP. In addition to entactin (7), these include fibrinogen, fibronectin, von Willebrand's factor, vitronectin, and collagen type IV (5). Whereas LRI-IAP may transduce the signals necessary for activation, other adhesive receptors may be involved in ligand binding. For example, domains within fibronectin other than the cell-binding domain appear to be involved in phagocyte adhesion (8), even though the RGD sequence within the cell-binding domains is responsible for the augmentation of phagocytosis by both monocytes (8,9) and PMN (5). In addition, fibrinogen (Fg)-stimulated and IAP, yet Fg also binds to a member of the .beta..sub.2 integrin family, .alpha..sub.m .beta..sub.2 (CD11b/CD18) (10-12). These facts raise the interesting possibility of integrin receptor cooperation in phagocyte activation.